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OBJECTIVES: To determine (1) the rate of positive cultures in presumed aseptic nonunions, (2) the rate and microbial spectrum of positive cultures that represented occult infection, and (3) rates of nonunion healing. DESIGN: Retrospective cohort study. SETTING: Tertiary referral center. PATIENTS SELECTION CRITERIA: Adult patients with a presumed aseptic nonunion treated with single-stage revision between 2002 and 2022. OUTCOME MEASURES AND COMPARISONS: The rate of positive cultures compared for 2 protocols: old: 1-2 samples cultured 7 days versus new: 5 samples cultured 14 days. The rate of positive cultures meeting occult infection criteria with the new protocol (≥2 samples with phenotypically indistinguishable microorganisms, or ≥1 sample with a high virulent microorganism). Nonunion healing rates between protocols and between groups based on culture results with the new protocol. RESULTS: One hundred seventy-nine patients were included. The rate of positive cultures was 14% (n = 15/105) with the old protocol and 51% (n = 38/74) with the new protocol (P < 0.001). With the new protocol, the rate of positive cultures meeting occult infection criteria was 19% (n = 14/74), and coagulase-negative staphylococci (48%) and Cutibacterium acnes (38%) were the most common microorganisms. Nonunion healing rates after the primary revision did not differ between protocols (old: 82% vs. new: 86%, P = 0.41) and groups based on culture result (sterile: 86% vs. occultly infected: 93%, P = 0.66). The final overall nonunion healing rate was 97%. CONCLUSIONS: Occult infections were identified in 1 in 5 presumed aseptic nonunions using a standardized protocol with 5 intraoperative samples cultured 14 days and were predominantly caused by slow growing, gram-positive microorganisms. The local spectrum and antimicrobial sensitivity of occult infections should be considered when developing empiric antimicrobial protocols. Patients with presumed aseptic nonunions can expect high healing rates, regardless of the culture result. LEVEL OF EVIDENCE: Diagnostic Level III. See Instructions for Authors for a complete description of levels of evidence.
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Fracturas no Consolidadas , Humanos , Estudios Retrospectivos , Masculino , Femenino , Persona de Mediana Edad , Fracturas no Consolidadas/microbiología , Fracturas no Consolidadas/cirugía , Adulto , Anciano , Curación de Fractura , Estudios de Cohortes , Resultado del Tratamiento , Infección de la Herida Quirúrgica/microbiología , Infección de la Herida Quirúrgica/diagnóstico , Reoperación , Fijación Interna de FracturasRESUMEN
INTRODUCTION: In pre-operatively presumed aseptic nonunions, the definitive diagnosis of infection relies on intraoperative cultures. Our primary objective was to determine (1) the rate of surprise positive intraoperative cultures in presumed aseptic long-bone nonunion (surprise positive culture nonunion), and (2) the rate of surprise positive cultures that represent infection vs. contamination. Secondary objectives were to determine the healing and secondary surgery rates and to identify cultured micro-organisms. MATERIALS AND METHODS: We performed a systematic literature search of PubMed, Embase and Cochrane Libraries from 1980 until December 2021. We included studies reporting on ≥ 10 adult patients with a presumed aseptic long-bone nonunion, treated with a single-stage surgical protocol, of which intraoperative cultures were reported. We performed a meta-analysis for: (1) the rates of surprise positive culture nonunion, surprise infected nonunion, and contaminated culture nonunion, and (2) healing and (3) secondary surgery rates for each culture result. Risk of bias was assessed using the QUADAS-2 tool. RESULTS: 21 studies with 2,397 patients with a presumed aseptic nonunion were included. The rate of surprise positive culture nonunion was 16% (95%CI: 10-22%), of surprise infected nonunion 10% (95%CI: 5-16%), and of contaminated culture nonunion 3% (95%CI: 1-5%). The secondary surgery rate for surprise positive culture nonunion was 22% (95%CI: 9-38%), for surprise infected nonunion 14% (95%CI 6-22%), for contaminated culture nonunion 4% (95%CI: 0-19%), and for negative culture nonunion 6% (95CI: 1-13%). The final healing rate was 98% to 100% for all culture results. Coagulase-negative staphylococci accounted for 59% of cultured micro-organisms. CONCLUSION: These results suggest that surprise positive cultures play a role in the clinical course of a nonunion and that culturing is important in determining the etiology of nonunion, even if the pre-operative suspicion for infection is low. High healing rates can be achieved in presumed aseptic nonunions, regardless of the definitive intraoperative culture result.
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Fijación Interna de Fracturas , Fracturas no Consolidadas , Adulto , Humanos , Estudios Retrospectivos , Fijación Interna de Fracturas/métodos , Staphylococcus , Fracturas no Consolidadas/cirugía , Curación de Fractura , Resultado del TratamientoRESUMEN
AIMS: Pharmacokinetic/pharmacodynamic target attainment of ceftriaxone is compromised in intensive care unit (ICU) patients and non-ICU hospitalized patients in Beira, Mozambique. Whether this also accounts for non-ICU patients in a high-income setting is unknown. We therefore assessed the probability of target attainment (PTA) of the currently recommended dosing regimen of 2 g every 24 h (q24h) in this patient group. METHODS: We performed a multicentre population pharmacokinetic study in hospitalized non-ICU adult patients empirically treated with intravenous ceftriaxone. During both the acute phase of infection (i.e. first 24 h of treatment) and convalescence, a maximum of 4 random blood samples were obtained per patient for ceftriaxone total and unbound concentration measurements. PTA was calculated using NONMEM and was defined as the percentage of patients of which the unbound ceftriaxone concentration exceeded the minimum inhibitory concentration (MIC) for >50% of the first dosing interval of 24 h. Monte Carlo simulations were performed to determine PTA for different estimated glomerular filtration rates (eGFR; CKD-EPI) and MICs. PTA >90% was considered adequate. RESULTS: Forty-one patients provided 252 ceftriaxone total and 253 unbound concentrations. The median eGFR was 65 mL/min/1.73 m2 (5th to 95th percentile 36-122). With the recommended dose of 2 g q24h, PTA >90% was achieved for bacteria with an MIC ≤2 mg/L. Simulations showed that PTA was insufficient for an MIC of 4 mg/L in case the eGFR was 122 mL/min/1.73 m2 (PTA 56.9%) and for an MIC of 8 mg/L regardless of eGFR. CONCLUSION: The PTA of 2 g q24h ceftriaxone dosing is adequate for common pathogens during the acute phase of infection in non-ICU patients.
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Antibacterianos , Ceftriaxona , Humanos , Adulto , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Cuidados Críticos , Pruebas de Sensibilidad Microbiana , Enfermedad Crítica/terapia , Método de MontecarloRESUMEN
Early detection of bacterial transmission and outbreaks in hospitals is important because nosocomial infections can result in health complications and longer hospitalization. Current practice to detect outbreaks uses genotyping methods amplified fragment length polymorphism (AFLP) and whole genome sequencing (WGS), which are not suitable methods for real-time transmission screening of both susceptible and resistant bacteria. The aim was to assess the typing technique Fourier transform infrared (FTIR) spectroscopy as real-time screening method to discriminate large amounts of susceptible and resistant bacteria at strain level when there is no evident outbreak in comparison with the WGS reference. Isolates of past hospital outbreak strains of Acinetobacter baumannii/calcoaceticus complex (n = 25), Escherichia coli (n = 31), Enterococcus faecium (n = 22), Staphylococcus aureus (n = 37) and Pseudomonas aeruginosa (n = 30) were used for validation of FTIR. Subsequently, Enterococcus faecalis (n = 106) and Enterococcus faecium (n = 104) isolates from weekly routine screening samples when no potential outbreak was present were analysed. FTIR showed reproducibility and congruence of cluster composition with WGS for A. baumannii/calcoaceticus complex and E. faecium outbreak isolates. The FTIR results of E. faecalis and E. faecium isolates from routine samples showed reproducibility, but the congruence of cluster composition with WGS was low. For A. baumannii/calcoaceticus complex and E. faecium outbreak isolates, FTIR appears to be a discriminatory typing tool. However, our study shows the discriminatory power is too low to screen real-time for transmission of E. faecium and E. faecalis at patient wards based on isolates acquired in routine surveillance cultures when there is no clear suspicion of an ongoing outbreak.
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Infección Hospitalaria , Enterococcus faecium , Infecciones por Bacterias Grampositivas , Análisis del Polimorfismo de Longitud de Fragmentos Amplificados , Infección Hospitalaria/epidemiología , Infección Hospitalaria/genética , Infección Hospitalaria/microbiología , Enterococcus faecium/genética , Genoma Bacteriano , Genotipo , Infecciones por Bacterias Grampositivas/epidemiología , Infecciones por Bacterias Grampositivas/genética , Infecciones por Bacterias Grampositivas/microbiología , Hospitales , Humanos , Reproducibilidad de los Resultados , Espectroscopía Infrarroja por Transformada de Fourier , Secuenciación Completa del Genoma/métodosRESUMEN
Staphylococcus pseudintermedius can be transmitted between dogs and their owners and can cause opportunistic infections in humans. Whole genome sequencing was applied to identify the relatedness between isolates from human infections and isolates from dogs in the same households. Genome SNP diversity and distribution of plasmids and antimicrobial resistance genes identified related and unrelated isolates in both households. Our study shows that within-host bacterial diversity is present in S. pseudintermedius, demonstrating that multiple isolates from each host should preferably be sequenced to study transmission dynamics.
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OBJECTIVES: Evaluation of the appropriateness of the duration of antimicrobial treatment is a cornerstone of antibiotic stewardship programs, but it is time-consuming. Furthermore, it is often restricted to antibiotics prescribed during hospital admission. This study aimed to determine whether mandatory prescription-indication registration at the moment of prescribing antibiotics enables reliable automated assessment of the duration of antibiotic therapy, including post-discharge duration, limiting the need for manual chart review to data validation. METHODS: Antibiotic prescription and admission data, from 1-6-2020 to 31-12-2021, were electronically extracted from the Electronic Medical Record of two hospitals using mandatory indication registration. All consecutively prescribed antibiotics of adult patients who received empiric therapy in the first 24 h of admission were merged to calculate the total length of therapy (LOT) per patient, broken down per registered indication. Endpoints were the accuracy of the data, evaluated by comparing the extracted LOT and registered indication with the clinical notes in 400 randomly selected records, and guideline adherence of treatment duration. Data were analysed using a reproducible syntax, allowing semi-automated surveillance. RESULTS: A total of 3,466 antibiotic courses were analysed. LOT was accurately retrieved in 96% of the 400 evaluated antibiotic courses. The registered indication did not match chart review in 17% of antibiotic courses, of which only half affected the assessment of guideline adherence. On average, in 44% of patients treatment was continued post-discharge, accounting for 60% (± 19%) of their total LOT. Guideline adherence ranged from 26 to 75% across indications. CONCLUSIONS: Mandatory prescription-indication registration data can be used to reliably assess total treatment course duration, including post-discharge antibiotic duration, allowing semi-automated surveillance.
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Cuidados Posteriores , Programas de Optimización del Uso de los Antimicrobianos , Adulto , Antibacterianos/uso terapéutico , Adhesión a Directriz , Humanos , Alta del PacienteRESUMEN
BACKGROUND: Bacteria produce volatile organic compounds (VOCs) during growth, which can be detected by colorimetric sensor arrays (CSAs). The SpecifAST® system (Specific Diagnostics) employs this technique to enable antibiotic susceptibility testing (AST) directly from blood cultures without prior subculture of isolates. The aim of this study was to compare the SpecifAST® AST results and analysis time to the VITEK®2 (bioMérieux) system. METHODS: In a 12-month single site prospective study, remnants of clinical positive monomicrobial blood cultures were combined with a series of antibiotic concentrations. Volatile emission was monitored at 37 °C via CSAs. Minimal Inhibitory Concentrations (MICs) of seven antimicrobial agents for Enterobacterales, Staphylococcus, and Enterococcus spp. were compared to VITEK®2 AST results. MICs were interpreted according to EUCAST clinical breakpoints. Performance was assessed by calculating agreement and discrepancy rates. RESULTS: In total, 96 positive blood cultures containing Enterobacterales, Staphylococcus, and Enterococcus spp. were tested (269 bug-drug combinations). The categorical agreement of the SpecifAST® system compared to the VITEK®2 system was 100% and 91% for Gram-negatives and Gram-positives, respectively. Errors among Gram-positives were from coagulase-negative staphylococci. Overall results were available in 3.1 h (±0.9 h) after growth detection without the need for subculture steps. CONCLUSION: The AST results based on VOC detection are promising and warrant further evaluation in studies with a larger sample of bacterial species and antimicrobials.
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BACKGROUND: Semi-quantitative bacterial culture is the reference standard to diagnose urinary tract infection, but culture is time-consuming and can be unreliable if patients are receiving antibiotics. Metagenomics could increase diagnostic accuracy and speed by sequencing the microbiota and resistome directly from urine. We aimed to compare metagenomics to culture for semi-quantitative pathogen and resistome detection from urine. METHODS: In this proof-of-concept study, we prospectively included consecutive urine samples from a clinical diagnostic laboratory in Amsterdam. Urine samples were screened by DNA concentration, followed by PCR-free metagenomic sequencing of randomly selected samples with a high concentration of DNA (culture positive and negative). A diagnostic index was calculated as the product of DNA concentration and fraction of pathogen reads. We compared results with semi-quantitative culture using area under the receiver operating characteristic curve (AUROC) analyses. We used ResFinder and PointFinder for resistance gene detection and compared results to phenotypic antimicrobial susceptibility testing for six antibiotics commonly used for urinary tract infection treatment: nitrofurantoin, ciprofloxacin, fosfomycin, cotrimoxazole, ceftazidime, and ceftriaxone. FINDINGS: We screened 529 urine samples of which 86 were sequenced (43 culture positive and 43 culture negative). The AUROC of the DNA concentration-based screening was 0·85 (95% CI 0·81-0·89). At a cutoff value of 6·0 ng/mL, culture positivity was ruled out with a negative predictive value of 91% (95% CI 87-93; 26 of 297 samples), reducing the number of samples requiring sequencing by 56% (297 of 529 samples). The AUROC of the diagnostic index was 0·87 (95% CI 0·79-0·95). A diagnostic index cutoff value of 17·2 yielded a positive predictive value of 93% (95% CI 85-97) and a negative predictive value of 69% (55-80), correcting for a culture-positive prevalence of 66%. Gram-positive pathogens explained eight (89%) of the nine false-negative metagenomic test results. Agreement of phenotypic and genotypic antimicrobial susceptibility testing varied between 71% (22 of 31 samples) and 100% (six of six samples), depending on the antibiotic tested. INTERPRETATION: This study provides proof-of-concept of metagenomic semi-quantitative pathogen and resistome detection for the diagnosis of urinary tract infection. The findings warrant prospective clinical validation of the value of this approach in informing patient management and care. FUNDING: EU Horizon 2020 Research and Innovation Programme.
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Metagenómica , Infecciones Urinarias , Antibacterianos/farmacología , Humanos , Metagenómica/métodos , Estudios Prospectivos , Análisis de Secuencia de ADN , Infecciones Urinarias/diagnósticoRESUMEN
BACKGROUND: We defined the frequency of respiratory community-acquired bacterial co-infection in patients with COVID-19, i.e. patients with a positive SARS-CoV-2 PCR or a COVID-19 Reporting and Data System (CO-RADS) score ≥ 4, based on a complete clinical assessment, including prior antibiotic use, clinical characteristics, inflammatory markers, chest computed tomography (CT) results and microbiological test results. METHODS: Our retrospective study was conducted within a cohort of prospectively included patients admitted for COVID-19 in our tertiary medical centres between 1-3-2020 and 1-6-2020. A multidisciplinary study team developed a diagnostic protocol to retrospectively categorize patients as unlikely, possible or probable bacterial co-infection based on clinical, radiological and microbiological parameters in the first 72 h of admission. Within the three categories, we summarized patient characteristics and antibiotic consumption. RESULTS: Among 281 included COVID-19 patients, bacterial co-infection was classified as unlikely in 233 patients (82.9%), possible in 35 patients (12.4%) and probable in 3 patients (1.1%). Ten patients (3.6%) could not be classified due to inconclusive data. Within 72 h of hospital admission, 81% of the total study population and 78% of patients classified as unlikely bacterial co-infection received antibiotics. CONCLUSIONS: COVID-19 patients are unlikely to have a respiratory community-acquired bacterial co-infection. This study underpins recommendations for restrictive use of antibacterial drugs in patients with COVID-19.
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Infecciones Bacterianas/epidemiología , COVID-19/diagnóstico , Coinfección/epidemiología , Infecciones Comunitarias Adquiridas/epidemiología , Hospitalización/estadística & datos numéricos , Neumonía/epidemiología , Adulto , Antibacterianos/uso terapéutico , Programas de Optimización del Uso de los Antimicrobianos , Infecciones Bacterianas/tratamiento farmacológico , Infecciones Bacterianas/microbiología , COVID-19/complicaciones , Estudios de Cohortes , Coinfección/tratamiento farmacológico , Infecciones Comunitarias Adquiridas/microbiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , SARS-CoV-2RESUMEN
Staphylococcus pseudintermedius is an important pathogen in dogs that occasionally causes infections in humans as an opportunistic pathogen of elderly and immunocompromised people. This study compared the genomic relatedness and antimicrobial resistance genes using genome-wide association study (GWAS) to examine host association of canine and human S. pseudintermedius isolates. Canine (n = 25) and human (n = 32) methicillin-susceptible S. pseudintermedius (MSSP) isolates showed a high level of genetic diversity with an overrepresentation of clonal complex CC241 in human isolates. This clonal complex was associated with carriage of a plasmid containing a bacteriocin with cytotoxic properties, a CRISPR-cas domain and a pRE25-like mobile element containing five antimicrobial resistance genes. Multi-drug resistance (MDR) was predicted in 13 (41%) of human isolates and 14 (56%) of canine isolates. CC241 represented 54% of predicted MDR isolates from humans and 21% of predicted MDR canine isolates. While it had previously been suggested that certain host-specific genes were present the current GWAS analysis did not identify any genes that were significantly associated with human or canine isolates. In conclusion, this is the first genomic study showing that MSSP is genetically diverse in both hosts and that multidrug resistance is important in dog and human-associated S. pseudintermedius isolates.
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BACKGROUND: The systemic response to an infection might influence the pharmacokinetics of antibiotics. To evaluate the desired possibility of an earlier (< 24 h) IV-to-oral switch therapy in febrile non-ICU, hospitalized patients, a systematic review was performed to assess the effect of the initial phase of a systemic infection on the bioavailability of orally administered antibiotics in such patients. METHODS: An electronic search was conducted in MEDLINE and Embase up to July 2020. Studies were selected when outcome data were collected during the initial stage of a febrile disease. Outcome data were (maximum) serum concentrations, time of achieving maximum serum concentration, and the area-under-the-plasma-concentration-time curve or bioavailability of orally administered antibiotics. Risk of bias was assessed. RESULTS: We identified 9 studies on 6 antibiotics. Ciprofloxacin was the most frequently studied drug. Outcomes of the studies were heterogeneous and generally had a high risk of bias. Three small studies, two on ciprofloxacin and one on clarithromycin, compared the pharmacokinetics of febrile patients with those of clinically recovered patients and suggested that bioavailability was not altered in these patients. Other studies either compared the pharmacokinetics in febrile patients with reported pharmacokinetic values from earlier studies in healthy volunteers (n = 2), or provided no comparison at all and were non-conclusive (n = 4). CONCLUSION: There is a clear knowledge gap regarding the bioavailability of orally administered antibiotics in non-ICU patients during the initial phase of a systemic infection. Well-designed studies on this topic are necessary to elucidate whether patients can benefit from the advantages of an earlier IV-to-oral switch.
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Antibacterianos/farmacocinética , Infecciones/tratamiento farmacológico , Administración Oral , Antibacterianos/uso terapéutico , Disponibilidad Biológica , Ciprofloxacina , Fiebre , HumanosRESUMEN
OBJECTIVE: There is unmet need for an easy, noninvasive urine collection method to diagnose urinary tract infections (UTIs) in nursing home residents suffering from urinary incontinence or cognitive impairments. UTIs are highly prevalent in nursing home residents, and urine specimen collection can be difficult. The objective of this study was to assess if urine specimens collected from super-absorbing incontinence pads (adult diapers) are a reliable collection method for UTI diagnosis. DESIGN: This was a paired noninferiority laboratory study, in which pairing refers to UTI diagnostics performed directly using clinical urine specimens (reference specimen) and indirectly using urine extracted from diapers (diaper specimen). SETTING AND PARTICIPANTS: In this study, remnants of 250 clinical urine specimens were used to assess noninferiority in diagnosing UTIs, based on a 1-sided type I error of 2.5%, a power of 90%, and a noninferiority margin of 15%. METHODS: Urine specimens were poured on super-absorbing disposable adult diapers and extracted after 3 hours, to use for dipstick urinalysis and bacterial culture. UTIs were defined as presence of leukocytes and a positive bacterial culture. Noninferiority was assessed by calculating a Wald-type test statistic. RESULTS: Noninferiority was established for diagnosing UTIs in diaper specimens, and for each of its components (dipstick leukocyte detection and bacterial culture positivity). Positive bacterial cultures were found in 72 (29.0%) diaper specimens compared with 65 (26.2%) reference specimens (difference -2.8%, 97.5% CI -7.1% to 1.5%). Leukocytes were present in 162 (64.8%) diaper specimens, compared with 175 (70.0%) reference specimens (difference -5.7%, 97.5% CI: -10.6% to -0.7%). CONCLUSION AND IMPLICATIONS: Our results on diagnosing UTIs, by dipstick analysis and bacterial cultures, using super-absorbing adult diapers are promising. Before translation into clinical practice, further studies are needed to evaluate the risk of bacterial contamination by wearing adult diapers, possibly resulting in overdiagnosis of UTI.
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Incontinencia Urinaria , Infecciones Urinarias , Adulto , Humanos , Pañales para la Incontinencia , Casas de Salud , Urinálisis , Infecciones Urinarias/diagnósticoRESUMEN
OBJECTIVES: Antimicrobial Stewardship Programs commonly have an in-hospital focus. Little is known about the quality of antimicrobial use in hospital outpatient clinics. We investigated the extent and appropriateness of antimicrobial prescriptions in the outpatient clinics of three hospitals. METHODS: From June 2018 to January 2019, we performed ten point prevalence surveys in outpatient clinics of one university hospital and two large teaching hospitals. All prophylactic and therapeutic prescriptions were retrieved from the electronic medical records. Appropriateness was defined as being in accordance with guidelines. Furthermore, we investigated the extent to which the dose was adjusted to renal function and documentation of an antibiotic plan in the case notes. RESULTS: We retrieved 720 prescriptions for antimicrobial drugs, of which 173 prescriptions (24%) were prophylactic. A guideline was present for 95% of prescriptions, of which the guideline non-adherence rate was 25.6% (n = 42/164) for prophylaxis and 43.1% (n = 224/520) for therapy. Of all inappropriate prescriptions (n = 266), inappropriate prescriptions for skin and soft tissue infections (n = 60/226) and amoxicillin-clavulanic acid (n = 67/266) made up the largest proportion. In only 13 of 138 patients with impaired or unknown renal function the dosage regimen was adjusted. Amoxicillin-clavulanic acid was the drug for which most often renal function was not taken into account. In 94.6% of prescriptions the antibiotic plan was documented. CONCLUSIONS: In hospital outpatient clinics, a substantial part of therapeutics were inappropriately prescribed. Amoxicillin-clavulanic acid was the most inappropriately prescribed drug, due to non-adherence to the guidelines and because dose adjustment to renal function was often not considered.
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Antibacterianos/farmacología , Profilaxis Antibiótica/estadística & datos numéricos , Programas de Optimización del Uso de los Antimicrobianos/métodos , Adhesión a Directriz/estadística & datos numéricos , Prescripción Inadecuada/estadística & datos numéricos , Riñón/fisiología , Combinación Amoxicilina-Clavulanato de Potasio/farmacología , Combinación Amoxicilina-Clavulanato de Potasio/uso terapéutico , Antibacterianos/uso terapéutico , Cálculo de Dosificación de Drogas , Registros Electrónicos de Salud , Hospitales de Enseñanza , Hospitales Universitarios , Humanos , Riñón/efectos de los fármacos , Pruebas de Función Renal , Países Bajos/epidemiología , Guías de Práctica Clínica como Asunto , PrevalenciaRESUMEN
Background: Recognition of nosocomial outbreaks with antimicrobial resistant (AMR) pathogens and appropriate infection prevention measures are essential to limit the consequences of AMR pathogens to patients in hospitals. Because unrelated, but genetically similar AMR pathogens may circulate simultaneously, rapid high-resolution molecular typing methods are needed for outbreak management. We compared amplified fragment length polymorphism (AFLP) and whole genome sequencing (WGS) during a nosocomial outbreak of vancomycin-resistant Enterococcus faecium (VRE) that spanned 5 months. Methods: Hierarchical clustering of AFLP profiles was performed using unweighted pair-grouping and similarity coefficients were calculated with Pearson correlation. For WGS-analysis, core single nucleotide polymorphisms (SNPs) were used to calculate the pairwise distance between isolates, construct a maximum likelihood phylogeny and establish a cut-off for relatedness of epidemiologically linked VRE isolates. SNP-variations in the vanB gene cluster were compared to increase the comparative resolution. Technical replicates of 2 isolates were sequenced to determine the number of core-SNPs derived from random sequencing errors. Results: Of the 721 patients screened for VRE carriage, AFLP assigned isolates of 22 patients to the outbreak cluster. According to WGS, all 22 isolates belonged to ST117 but only 21 grouped in a tight phylogenetic cluster and carried vanB resistance gene clusters. Sequencing of technical replicates showed that 4-5 core-SNPs were derived by random sequencing errors. The cut-off for relatedness of epidemiologically linked VRE isolates was established at ≤7 core-SNPs. The discrepant isolate was separated from the index isolate by 61 core-SNPs and the vanB gene cluster was absent. In AFLP analysis this discrepant isolate was indistinguishable from the other outbreak isolates, forming a cluster with 92% similarity (cut-off for identical isolates ≥90%). The inclusion of the discrepant isolate in the outbreak resulted in the screening of 250 patients and quarantining of an entire ward. Conclusion: AFLP was a rapid and affordable screening tool for characterising hospital VRE outbreaks. For in-depth understanding of the outbreak WGS was needed. Compared to AFLP, WGS provided higher resolution typing of VRE isolates with implications for outbreak management.
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Análisis del Polimorfismo de Longitud de Fragmentos Amplificados/métodos , Infección Hospitalaria/microbiología , Infecciones por Bacterias Grampositivas/diagnóstico , Enterococos Resistentes a la Vancomicina/aislamiento & purificación , Secuenciación Completa del Genoma/métodos , Proteínas Bacterianas/genética , Portador Sano/diagnóstico , Portador Sano/microbiología , Análisis por Conglomerados , Brotes de Enfermedades , Enterococcus faecium/clasificación , Enterococcus faecium/genética , Enterococcus faecium/aislamiento & purificación , Genoma Bacteriano , Humanos , Tipificación Molecular , Filogenia , Polimorfismo de Nucleótido Simple , Estudios Retrospectivos , Centros de Atención Terciaria , Factores de Tiempo , Enterococos Resistentes a la Vancomicina/clasificación , Enterococos Resistentes a la Vancomicina/genéticaRESUMEN
BACKGROUND: Invasive aspergillosis (IA) is a life-threatening opportunistic mycosis that occurs in some people with a compromised immune system. The serum galactomannan enzyme-linked immunosorbent assay (ELISA) rapidly gained widespread acceptance as part of the diagnostic work-up of a patient suspected of IA. Due to its non-invasive nature, it can be used as a routine screening test. The ELISA can also be performed on bronchoalveolar lavage (BAL), allowing sampling of the immediate vicinity of the infection. The invasive nature of acquiring BAL, however, changes the role of the galactomannan test significantly, for example by precluding its use as a routine screening test. OBJECTIVES: To assess the diagnostic accuracy of galactomannan detection in BAL for the diagnosis of IA in people who are immunocompromised, at different cut-off values for test positivity, in accordance with the Cochrane Diagnostic Test Accuracy Handbook. SEARCH METHODS: We searched three bibliographic databases including MEDLINE on 9 September 2016 for aspergillosis and galactomannan as text words and subject headings where appropriate. We checked reference lists of included studies for additional studies. SELECTION CRITERIA: We included cohort studies that examined the accuracy of BAL galactomannan for the diagnosis of IA in immunocompromised patients if they used the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) classification as reference standard. DATA COLLECTION AND ANALYSIS: Two review authors assessed study quality and extracted data. Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) was used for quality assessment. MAIN RESULTS: We included 17 studies in our review. All studies except one had a high risk of bias in two or more domains. The diagnostic performance of an optical density index (ODI) of 0.5 as cut-off value was reported in 12 studies (with 1123 patients). The estimated sensitivity was 0.88 (95% confidence interval (CI) 0.75 to 1.00) and specificity 0.81 (95% CI 0.71 to 0.91). The performance of an ODI of 1.0 as cut-off value could be determined in 11 studies (with 648 patients). The sensitivity was 0.78 (95% CI 0.61 to 0.95) and specificity 0.93 (95% CI 0.87 to 0.98). At a cut-off ODI of 1.5 or higher, the heterogeneity in specificity decreased significantly and was invariably >90%. AUTHORS' CONCLUSIONS: The optimal cut-off value depends on the local incidence and clinical pathway. At a prevalence of 12% a hypothetical population of 1000 patients will consist of 120 patients with IA. At a cut-off value of 0.5 14 patients with IA will be missed and there will be 167 patients incorrectly diagnosed with IA. If we use the test at a cut-off value of 1.0, we will miss 26 patients with IA. And there will be 62 patients incorrectly diagnosed with invasive aspergillosis. The populations and results were very heterogeneous. Therefore, interpretation and extrapolation of these results has to be performed with caution. A test result of 1.5 ODI or higher appears a strong indicator of IA.
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Aspergilosis/diagnóstico , Líquido del Lavado Bronquioalveolar/microbiología , Huésped Inmunocomprometido , Mananos/sangre , Aspergilosis/inmunología , Biomarcadores/sangre , Galactosa/análogos & derivados , Humanos , Infecciones Fúngicas Invasoras , Ensayos Clínicos Controlados Aleatorios como Asunto , Sensibilidad y EspecificidadRESUMEN
Tuberculosis is a devastating infectious disease causing many deaths worldwide. Recent investigations have implicated neutrophil extracellular traps (NETs) in the host response to tuberculosis. The aim of the current study was to obtain evidence for NETs release in the circulation during human tuberculosis. For this we measured the plasma concentrations of nucleosomes in conjunction with neutrophil elastase, in 64 patients with active pulmonary tuberculosis and 32 healthy controls. Patients with active tuberculosis had elevated plasma levels of nucleosomes and elastase when compared with local healthy blood donors. Furthermore nucleosome and elastase levels showed a positive correlation. These findings provide the first evidence for the release of NETs in the circulation of patients with active pulmonary tuberculosis.
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Trampas Extracelulares/metabolismo , Mycobacterium tuberculosis/metabolismo , Neutrófilos/metabolismo , Tuberculosis Pulmonar/sangre , Adulto , Femenino , Humanos , Masculino , Activación Neutrófila/fisiología , Tuberculosis Pulmonar/diagnóstico , Adulto JovenRESUMEN
Hard-tick-borne relapsing fever (HTBRF) is an emerging infectious disease throughout the temperate zone caused by the relapsing-fever spirochete Borrelia miyamotoi Antibiotic treatment of HTBRF is empirically based on the treatment of Lyme borreliosis; however, the antibiotic susceptibility of B. miyamotoi has not been studied to date. Thus, we set out to determine the in vitro antimicrobial susceptibility of B.miyamotoi A microdilution method with 96-well microtiter plates was used to determine the antibiotic susceptibilities of two B.miyamotoi strains isolated on two different continents (Asia and North America), two Borrelia burgdorferisensu lato strains, and one Borrelia hermsii isolate for purposes of comparison. The MIC and minimal bactericidal concentration (MBC) were determined by both microscopy and colorimetric assays. We were able to show that relative to the B. burgdorferi sensu lato isolates, both B.miyamotoi strains and B. hermsii demonstrated greater susceptibility to doxycycline and azithromycin, equal susceptibility to ceftriaxone, and resistance to amoxicillin in vitro The MIC and MBC of amoxicillin for B. miyamotoi evaluated by microscopy were 16 to 32 mg/liter and 32 to 128 mg/liter, respectively. Since B. miyamotoi is susceptible to doxycycline, azithromycin, and ceftriaxone in vitro, our data suggest that these antibiotics can be used for the treatment of HTBRF. Oral amoxicillin is currently used as an alternative for the treatment of HTBRF; however, since we found that the B. miyamotoi strains tested were resistant to amoxicillin in vitro, this issue warrants further study.
Asunto(s)
Amoxicilina/farmacología , Antibacterianos/farmacología , Azitromicina/farmacología , Borrelia/efectos de los fármacos , Ceftriaxona/farmacología , Doxiciclina/farmacología , Fiebre Recurrente/tratamiento farmacológico , Animales , Asia , Borrelia/clasificación , Borrelia/aislamiento & purificación , Farmacorresistencia Bacteriana , Humanos , Ratones , Pruebas de Sensibilidad Microbiana , América del Norte , Fiebre Recurrente/microbiologíaAsunto(s)
Descontaminación/métodos , Tracto Gastrointestinal , Orofaringe , Neumonía Asociada al Ventilador/prevención & control , Administración Oral , Antibacterianos/uso terapéutico , Estudios de Cohortes , Enfermedad Crítica/terapia , Femenino , Humanos , Unidades de Cuidados Intensivos , Masculino , Neumonía Asociada al Ventilador/tratamiento farmacológico , Neumonía Asociada al Ventilador/epidemiología , Estudios ProspectivosRESUMEN
BACKGROUND: The prophylactic use of antimicrobial agents to prevent infections in non-surgical situations has hardly been investigated. We investigate the extent, indications and appropriateness of antimicrobial prophylaxis given outside the operating room in a tertiary care hospital. METHODS: Four point-prevalence surveys were conducted in which all inpatients on that day were screened for the use of prophylactic antimicrobials: medical prophylaxis, prophylaxis around non-surgical interventions and surgical prophylaxis given on the ward. The primary endpoint was the extent of prophylaxis relative to the total number of antimicrobial prescriptions. We also investigated per prescription the presence of a (local) protocol and adherence to these protocols. RESULTS: We registered in total 1020 antimicrobial prescriptions, of which 317 (31.1%) were given as prophylaxis. 827/1020 were antibiotic prescriptions. Of these antibiotic prescriptions, 17.0% was medical prophylaxis, 2.7% prophylaxis around non-surgical interventions and 6.9% surgical prophylaxis administered on a ward. For medical antibiotic prophylaxis, a protocol was present in 125 of 141 prescriptions (88.7%); the protocol was followed in 118 cases (94.4%). For prophylaxis around non-surgical interventions and surgical prophylaxis on the wards, protocol presence and adherence rates were 59.1% and 92.3%, and 73.3% and 97.6% respectively. Of the 96 antiviral and 97 antifungal prescriptions, 42.7% and 57.8%, respectively, were medical prophylaxis, of which 95.1 and 96.3% were prescribed according to protocols respectively. CONCLUSIONS: Antimicrobial prophylaxis outside the operating theatre is responsible for a considerable part of total in-hospital antimicrobial use. For most prescriptions there was a protocol and adherence to the protocols was high. The main targets for improvement were prophylaxis around non-surgical interventions and surgical prophylaxis given on the ward.